Subtype Differences in Major Adverse Liver Outcomes and Cardiovascular Events and Mortality in Steatotic Liver...

The natural history of steatotic liver disease (SLD)-including major adverse liver outcomes (MALO), major adverse cardiovascular events (MACE), and all-cause mortality-remains inadequately defined in population-based settings.

We sought to quantify their incidence and compare risks across SLD subtypes.

We evaluated 244,760 UK Biobank participants, assessing metabolic dysfunction-associated SLD (MASLD), metabolic dysfunction and alcohol-associated liver disease (MetALD), or alcohol-associated liver disease (ALD), and examined outcomes across these subtypes.

Among the cohort, 47,949 (19.6%) had MASLD, 23,000 (9.4%) had MetALD, and 8085 (3.3%) had ALD. Of the 79,034 individuals with SLD (mean age 57.2; 72.4% female; 98.0% White), the incidence rates of MALO (per 1,000 person-years) were 1.91 for MASLD, 2.35 for MetALD, and 5.80 for ALD during a median follow-up of 13.5 years. Corresponding rates for MACE were 14.88, 15.48, and 19.36, and for all-cause mortality were 12.99, 13.59, and 20.93. After adjustment, ALD (hazard ratio [HR], 2.95; 95% CI, 2.64-3.29) and MetALD (HR, 1.23; 95% CI, 1.11-1.36) were associated with higher MALO risk than MASLD. ALD also showed higher risks of MACE and mortality than MetALD (MACE: HR, 1.17; 95% CI, 1.10-1.24; mortality: HR, 1.49; 95% CI, 1.41-1.58) or MASLD (MACE: HR, 1.17; 95% CI, 1.11-1.24; mortality: HR, 1.52; 95% CI, 1.44-1.60), whereas MetALD and MASLD showed no differences.

In the United Kingdom, ALD exhibited the highest liver, cardiovascular, and mortality risks, while MASLD and MetALD had similar cardiovascular and survival profiles but differed in liver-related risk.